Examples



mdbootstrap.com



 
Статья
2020

“Triple” mutual prodrug based on 2-methoxyestradiol: synthesis and biotesting in vitro


E. A. LavrushkinaE. A. Lavrushkina, V. M. ShibilevV. M. Shibilev, N. A. ZefirovN. A. Zefirov, E. F. ShevtsovaE. F. Shevtsova, P. N. ShevtsovP. N. Shevtsov, S. A. KuznetsovS. A. Kuznetsov, O. N. ZefirovaO. N. Zefirova
Российский химический вестник
https://doi.org/10.1007/s11172-020-2798-3
Abstract / Full Text

Ester of the tubulin ligand, 2-methoxyestradiol, with two molecules of DNA alkylating agent chlorambucil was proposed as a “triple” mutual prodrug for blocking rapid metabolism of the initial steroid. The target conjugate was synthesized via the Steglich esterification. The biotesting results demonstrate a very low cytotoxicity to cancer and conditionally normal cells (EC50 ~100 μmol L−1), a weak inhibition of the cell growth (A549: 20%/48 h), no stimulation of apoptosis, and no influence on the microtubule morphology of human lung carcinoma A549 cells and the ability to increase the rate of microtubule assembling. The sharp distinction of these properties from those for the initial 2-methoxyestradiol and chlorambucil molecules indicates that the synthesized prodrug is stable in vitro and demonstrates an expediency of its further testing in vivo.

Author information
  • Department of Chemistry, M. V. Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991, Moscow, Russian FederationE. A. Lavrushkina, N. A. Zefirov & O. N. Zefirova
  • Department of Fundamental Medicine, M. V. Lomonosov Moscow State University, Build. 1, 27 Lomonosovsky prosp., 119991, Moscow, Russian FederationV. M. Shibilev
  • Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severnyi proezd, 142432, Chernogolovka, Moscow Region, Russian FederationN. A. Zefirov, E. F. Shevtsova, P. N. Shevtsov & O. N. Zefirova
  • Institute of Biological Sciences, University of Rostock, D-18059, Rostock, GermanyS. A. Kuznetsov
References
  1. C. G. Wermuth, C. R. Ganellin, P. Lindberg, L. A. Mitscher, Pure Appl. Chem., 1998, 70, 1129.
  2. B. S. Kumar, D. S. Raghuvanshi, M. Hasanain, S. Alam, J. Sarkar, K. Mitra, F. Khan, A. S. Negi, Steriods, 2016, 110, 9.
  3. N. A. Zefirov, O. N. Zefirova, Russ. tJ. Org. Chem., 2015, 51, 1207.
  4. M. P. Leese, F. L. Jourdan, M. R. Major, W. Dohle, E. Hamel, E. Ferrandis, A. Fiore, Ph. G. Kasprzyk, B. V. L. Potter, ChemMedChem, 2014, 9, 85.
  5. E. V. Nurieva, N. A. Zefirov, A. V. Mamaeva, Y. K. Grishin, S. A. Kuznetsov, O. N. Zefirova, Mendeleev Commun., 2017, 27, 240.
  6. S. Kambhampati, R. A. Rajewski, M. Tanol, I. Haque, A. Das, S. Banerjee, S. Jha, D. Burns, E. Borrego-Diaz, P. J. Van Veldhuizen, S. K. Banerjee, Mol. Cancer Ther., 2013, 12, 255.
  7. Y. Chen, Y. Jia, W. Song, L. Zhang, Front. Pharmacol., 2018, 9, 1453.
  8. A. Gupta, P. Saha, C. Descoteaux, V. Leblanc, E. Asselin, G. Berube, Bioorg. Med. Chem. Lett., 2010, 20, 1614.
  9. E. V. Nurieva, N. A. Zefirov, A. V. Mamaeva, B. Wobith, S. A. Kuznetsov, O. N. Zefirova, Russ. Chem. Bull., 2018, 67, 688.
  10. T. Mosmann, J. Immunol. Meth., 1983, 65, 55.
  11. N. A. Zefirov, E. A. Lavrushkina, S. A. Kuznetsov, O. N. Zefirova, Biomed. Khim. [Biomedical Chemistry], 2019, 65, 86 (in Russian).
  12. R. K. Singh, D. N. Prasad, T. R. Bhardwaj, Med. Chem. Res. 2015, 24, 1534.
  13. Zh. Wang, D. Yang, A. K. Mohanakrishnan, Ph. E. Fanwick, P. Nampoothiri, E. Hamel, M. Cushman, J. Med. Chem., 2000, 43, 2419.
  14. M. D. Wittman, J. F. Kadow, D. M. Vyas, F. L. Lee, W. C. Rose, B. H. Long, C. Fairchild, K. Johnston, Bioorg. Med. Chem. Lett., 2001, 11, 811.
  15. B. Coggiola, F. Pagliai, G. Allegrone, A. A. Genazzani, G. C. Tron, Bioorg. Med. Chem. Lett., 2005, 15, 3551.
  16. S. O. Bachurin, E. F. Shevtsova, G. F. Makhaeva, V. V. Grigoriev, N. P. Boltneva, N. V. Kovaleva, S. V. Lushchekina, P. N. Shevtsov, M. E. Neganova, O. M. Redkozubova, E. V. Bovina, A. V. Gabrelyan, V. P. Fisenko, V. P. Sokolov, A. Y. Aksinenko, V. Echeverria, G. E. Barreto, G. Aliev, Sci. Rep., 2017, 7, 45627.
  17. P. N. Shevtsov, E. F. Shevtsova, G. Sh. Burbaeva, S. O. Bachurin, Bull. Exp. Biol. Med., 2006, 141, 265.
  18. O. N. Zefirova, H. Lemcke, M. Lantow, E. V. Nurieva, B. Wobith, G. E. Onishchenko, A. Hoenen, G. Griffiths, N. S. Zefirov, S. A. Kuznetsov, ChemBioChem, 2013, 14, 1444.